Posted
by
kdawson
on Sunday January 18, 2009 @09:19PM
from the gotta-have-heart dept.

mmmscience brings us news of a new study, published in Nature Genetics by an international team of scientists, that tells a scary story: globally, 1% of the population carry a gene mutation that is almost guaranteed to lead to some form of heart problems. On the Indian subcontinent, the prevalence is 4%. The mutation is a 25-letter deletion of DNA data on the heart protein gene MYBPC3, believed to have arisen in India 30,000 years ago. The researchers say that the mutation wasn't selected out of the population because its effects don't occur until after the childbearing years. The article mentions a prediction that "by 2010 India's population will suffer approximately 60% of the world's heart disease."

That's one way of looking at it. Then again, maybe these people will end up in hospital and get some (expensive) medical treatment rather than just dropping dead unannounced the moment they stop working, giving Indea a competitive disadvantage.

Or better yet, childhood diagnosis with this particular condition would merit lifetime treatment with statins and aggressive control of other modifying factors. Prevent these kids from smoking, get them in a daily exercise habit, teach them a good diet, and monitor and aggressively treat for diabetes and hypertension if/when they appear. Except for the genetic test itself, the rest of that is cheaper than spit. Even in the US, the real cost of the blood tests and medicines would be less than $200 annually. Add two NP visits and its maybe $400 annually. The cost in India would obviously be even cheaper.

However what is expensive is the political will to prevent smoking in children. Its also politically expensive to have cheap and effective public health prevention programs. Heaven forbid you give medicines or pap smears to people who don't have insurance or money.... why.... it.... would be an ENTITLEMENT!

I always find posts like this vaguely disturbing. It's worded as if these people are almost lucky. As if this life threatening disease is somehow a gift so that they will have plenty of incentive to live healthy.

Why not say: "Or better yet, someone will come up with a cheap cure that isn't some tailor made weekly supplement drug designed to make pharma corps money until the patient dies."

Or better yet, someone will come up with a cheap cure that isn't some tailor made weekly supplement drug designed to make pharma corps money until the patient dies.

The whole "drug companies want to keep you alive and dependant, not cured" thing sounds a lot like a bogus conspiracy theory to me. I know next to nothing about medicine, and I'm open to the possibility that I'm totally wrong.

First of all, I never hear any concrete examples, which is a good sign.

Second, drug companies aren't the CIA, when they do things wrong, like testing in 3rd world countries without real informed consent, it becomes public knowledge before too long. If they were sitting on an effectiv

but it's not heartening for the fight against heart disease to keep plodding on with little obvious progress in the span of time it takes for half a dozen new anti-ED drugs to hit the market.You do realize that heart disease research is where the ED drugs came from right? An interesting side-effect of the heart disease treatment lead to the discovery of Viagra. So it's not like there's just a room full of scientists thinking how can I make people turgid instead of curing some real life threatening disease.

People are more likely to do something when they have a higher risk to be effected.

Not always. Sometimes people take a defeatist attitude. It depends on how you frame that risk to the patient and how the patient sees it. A good example of such defeatism (and general adolescent 'fuck you' attitude) is kids with CF who start smoking.

there are more kinds of heart disease than coronary artery disease you know. this particular gene predisposes one to cardiomyopathy, not atherosclerosis. so your treatment plan would just have the effect of making these patients miserable for 40 years before they keeled over from heart failure.

The problem with India is that they have banned so many things in the past for dubious reasons and the enforcement is so corrupt that people tend to view any ban or issue with the government officials as a problem to be routed around with a bribe. The Indian people are so used to working around and over government regulations that even worthwile ones tend to be ingored at convenience in India.

India cannot support hundreds of millions of elderly pensioners. Long-term this will probably be a competitive advantage over China.

I don't know where you come from, but usually people in modern civilizations make an effort to help people live. Why don't we just kill everyone over 70? Or at least refuse them medical treatment? Or how about eliminating all forms of pension? That's a good competitive advantage.

I actually know one survived this problem with a heart transplant. You are really a lucky one in those unfortunate, most people with this problem died before doctors can diagnose this problem or even before seeing a doctor. I heard that there were only about 300 diagnosed cases (including those failed to get a heart transplant).

Best wishes. I know how painful and stressful it can be, but you are really the lucky one already, just one more step and you can live a common life again.

Giant cells seem to be a function of the body to fight off infections. I have a feeling, that in the future, we will find out that many diseases are caused/triggered by viral infections, along with some failure of a tumor suppressor gene.

One of my patients had a heart transplant 20+ years ago and is doing great, so things look really good for you, once ya do the engine change.

Yeah, those bloodsuckers will happily take your premiums year after year, until you actually start to cost them money. Then they find ways to get rid of you. Now, Federal Law in the U.S. says they can't just drop you arbitrarily, but they can jack your premiums up to the point where you can no longer pay. That happened to my Dad: he paid Aetna for decades and hardly used them... then when he became seriously ill they ramped up his premiums to about $20,000 a year, so we had give them up, and of course nobody else would insure him for less. Fortunately (and I use the term loosely) he suffered total renal failure and ended up on dialysis. That's one of the few medical conditions that will automatically give you Medicare at any age (he was 62 when he died.) If you're in any kind of a similar situation, man, I feel for you.

What truly torques me into a preztel are the routine conflicts-of-interest and general corruption/collusion between insurance companies and medical suppliers. It's really obscene... and billions could be saved (along with many lives) if insurance carriers would spend a little money trying to reduce waste and outright fraud. For example, I had a girlfriend whose father had to go in for an MRI at one point. Fairly routine, except that the hospital billed their insurance for two MRIs, both listed as being on the same day at the same time. One could say, well, hell, it's not your own money at stake, but when you have a lifetime cap and are getting old... well. So her mother calls the insurance company (repeatedly) to complain about this fraudulent billing (at the time an MRI was very expensive.) She was told (repeatedly!) that "we have to go by what the hospital says."

My mom needs a hearing aid. When she recently had to get a new one, this is what the hearing aid vendor told her. The MSRP is $12k (each!). If you have insurance, they bill them at $8k each. But, if you don't have insurance, they'll give you a "discount" and sell them to you directly at $3k each. They probably still make money on them at $3k, but they get to bilk an extra $5k out of the insurance company if they can... Since they never actually charge the "MSRP," I can only surmise that it's that high because they have to "discount" it for the insurance companies by a certain percent.

I've been lucky enough to be pretty healthy, but every time I can remember seeing a doctor for something relatively minor, they found ways to use "creative wording" to bill my insurance the maximum amount possible.

EG. One time, I had a wax build-up in my left ear. I woke up one morning and could barely hear out of it. The clinic I went to charged me for the nurse who tried to remove it, but wasn't very skilled at using the rinsing tool that's used to clean out the ear. So she went to ask for

How about a better one.. what about the fact men pay about 25% more than women for health, life, and auto?

Funny how some forms of discrimination are allowed, but not based on genetic tests.. OH WAIT, IT IS ALLOWED, they can examine your records, determine tests showed genetic predisposition, deny coverage.

The Act prohibits group health plans and health insurers from denying coverage to a healthy individual or charging that person higher premiums based solely on a genetic predisposition to developing a disease in the future.

"we noticed you paid for a few more tests recently, and have been sick more often"

there go your rates, or "im sorry your coverage is denied"

WOW.. I haven't seen a loophole this big for abuse since the anti-circumvention clause of the DMCA

globally, 1% of the population carry a gene mutation that is almost guaranteed to lead to some form of heart problems.

World population is about 6.7B. Total number of people with this mutation in the world:1% * 6.7B = 67M.

On the Indian subcontinent, the prevalence is 4%.

According to Wikipedia, the subcontinent "accounts for about 40 percent of Asia's population," which is 4B. Total number of people there with this mutation:4% * 40% * 4B = 64M

So, the percentage of people NOT on the Indian subcontinent that carry this mutation is:(67M - 64M) / (6.7B - 40%*4B) = 0.06%.

With such a great geographical disparity in incidence, using the global 1% figure to generate the headline of "1 in 100 carry mutation" is incredibly misleading.

The linked article is quite a bit better. It's titled "The heart disease mutation carried by 60 million," and focuses on this as being primarily an Indian problem. Somehow I'm not surprised to see kdawson as the editor on this one.

Yup. Pretty bad. Especially if you read the title or the abstract of the article in Nature Genetics.

A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia

Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown...Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart fa

the thing i hate about these nonsense genetic claims, is that there is a 100% probability you are going to die of something. so claiming 60% of people will die of heart disease (because heart failure and cancer are what take out most of our population) is like pronouncing you have discovered people grow old and die. what would be more accurate, but you will never see them do it, is to tell us who will die a PREMATURE death due to heart disease. the reason they won't do it is there is far more to what kills you than genetics and admitting as much might see grant money going else where.

what would be more accurate, but you will never see them do it, is to tell us who will die a PREMATURE death due to heart disease.

They sorta do. From TFA:

Scientists express this genetic risk as an odds ratio, where 1.2 would be a small effect and 2.0 a large one. For the MYBPC3 mutation, the odds ratio is almost off-scale, a staggering 7.0. Carriers usually show few symptoms until middle age, but after that age most are symptomatic and suffer from a range of effects, at worst sudden cardiac death.

huge numbers of people, even if small compared to the total number of people ever

It isn't as small as you might think. I don't remember the exact figures, but explosive population growth during the 20th and 21st centuries have led to a situation where the proportion of people still alive to those who have ever lived is surprisingly high.

Apparently current estimates place total number of people who have ever lived at around 100 billion. (out of which 6 billion is still quite high, though nowhere near popular myth "there are currently more poeple alive than have lived in the past":p )

Now that they've identified the problem, there's a reasonable chance that it can be treated. It might well require a weekly pill or some such, or even a shot, as RNA is too delicate to trust to the gut. But many such things are treatable already.

India has a flourishing medical community, including many pharmaceutical companies. I would expect them to jump on this quickly.

Now that they've identified the problem, there's a reasonable chance that it can be treated. It might well require a weekly pill or some such, or even a shot, as RNA is too delicate to trust to the gut. But many such things are treatable already.

FTFA: Carriers could be identified at a young age by genetic screening and adopt a healthier lifestyle.

IMO, that is some pie in the sky thinking.One of the top problems in the medical field is patient non-compliance.It's hard enough for a doctor to get their patients to finish taking a regimen of antibiotics, much less change to a healthier lifestyle.

The gene is responsible for Hypertrophic Cardio Myopathy [wikipedia.org]. HCM causes a thickening of the heart muscle and is often treated with medication, installation of an ICD [wikipedia.org] to mitigate the chance of sudden cardiac death and for those with obstructions, a myectomy [mayoclinic.org] can be done. Something like 5% of HCM cases will require a heart transplant.

Gene testing is something I'll be doing soon to identify exactly which mutation I have, several are responsible for HCM. Once that's done I'll have my kids tested so they don't have to go through the annual testing that they are beginning this year.

HCM is the number one cause of sudden cardiac death in people under the age of 30. You may have heard of professional or college level athletes dying on the court/field/ whatever. This is usually the cause.

I am in otherwise excellent condition. I have had a "healthy lifestyle" my whole life but now I can't walk up a flight of stairs without experiencing shortness of breath. I will likely have a myectomy [mayoclinic.org] this year.

The good news is that this operation has a very high success rate. Another piece of good news is that if you have HCM and are treated by a specialist your life expectancy jumps back up to that of the general population.

I'm glad that it's surgically treatable. What I'm hoping for, and suggesting, however, is a treatment for youngsters that will prevent the disease from developing. Clearly for adults it's too late for treatments that only take effect while you are growing up, i.e., while the organs are still building themselves and naturally increasing in size.

The researchers say that the mutation wasn't selected out of the population because its effects don't occur until after the childbearing years.

It's not that simple though. One's roll in the gene pool does not (indirectly) end when you lose fertility. The grandparents care for the children, and in doing so, their children's (related) DNA is encouraged. Also, unlike women, men don't have menopause, and are also affected by heart disease etc and a man's DNA is just as genetically useful at 60 as it was at 25.

That's an interesting development in a well-known genetic heart defect. Myosin binding protein C is well known, and mutations in MYPBC3 are one of the most common causes of heart defects in humans (and cats).

If parents are comfortable with prenatal testing and abortion, this genetic defect could be effectively eliminated, in the same way that Down's syndrome has declined dramatically. In principle, the MYPBC3 defect would eventually be eliminated from the population.

MYPBC3 is a pretty cool protein, BTW. It connects the light chains and the heavy chains that make up muscle fibers. Obviously if the proteins that make up muscle fibers come apart you're going to have problems.

Another common cause of heart defects is protein called beta-myosin heavy chain (MYH7). MYH7 also comes out of the heavy chain. It's the one that looks like a bean pod. It looks a little like this:____________====P==P====

James Watson has 20 genes in the 5000 disease gene database according to an article in Nature last year. In last week's Sunday's New York Times Steve Pinker, one of the first 13 people to have their genomes fully sequenced, said he had several unexpressed bad genes, including a gene for baldness.

I believe Congress is planning a law that says insurance companies cant deny on basis of genome, due to the current lack of understanding.

India has a population of C. 1.1 billion, to a world total of 6.7 or so. If 1.1 billion have a 4% prevalence, that is ~44 million. If 6.7 billion have an overall 1% prevalence, that would be ~67 million. 67-44 gives us 23 million affected among the 5.6 billion non-indian humans. That makes for ~.4% among non-indians. This assumes, of course, that the 1% number is worldwide, rather than non-indian worldwide. 1/10th the risk is fairly dramatic; but.4% is only slightly less than 1 in 200 people, which is very much in the "somebody, probably several people, you know and or work with have it right now" territory rather than the "vague abstract risk" territory.

Most of the population affected outside India are probably Indian or have a significant Indian ancestry. This doesn't change your numbers, but shows that the risk is actually much higher or lower depending on your social group.

I did a quick read of the Nature Genetics letter [nature.com] and, as far as I can tell, it makes no claims as to the worldwide frequency of the allele (actually a micro-deletion). Accurately measuring allele frequencies for the world's population is not something that most studies are adequately designed for, so it's not surprising that they don't provide an estimate.
Here's what they have to say about the deletion's frequency outside of India.

The presence of this deletion in many Indian populations with varied geographical and ancestral backgrounds raises the question of how geographically widespread it is outside India. We therefore also analyzed 63 world population samples, comprising 2,085 indigenous individuals from 26 countries including all five continents. The 25-bp deletion was observed in Pakistan, Sri Lanka, Indonesia and Malaysia, (all heterozygotes) but was absent from other samples. Thus, the deletion is a common variant in individuals from South Asia, present in Southeast Asia, but undetectable elsewhere (Fig. 3 and Supplementary Table 5 online).

The supplementary materials give the sample sizes for each of the ethnic groups that were sampled and the number of deletion carriers. Most of the individual samples are small, but in the aggregate they do strongly suggest that the deletion is practically non-existent outside of South Asia and a few neighboring areas.

This does raise the question of how the media got this 1% prevalence estimate, unless I completely missed it in the article. In general, media outlets don't report the contents of peer-reviewed articles, they report the contents of press releases that accompany (or precede) the articles.

Don't worry, 10% of north americans and europeans suffer from moneyitis, the deadly disease of insurance companies paying doctors to overlook symptoms. Incurable diseases are much cheaper then curable ones.

On the flip-side, we've got pharmaceutical companies making billions off diseases we don't necessarily have...

1) If you are going into medicine for the money and are pre-med now, you are basically going to end up in the same situation that all those kids coming out of Harvard with MBAs expecting to make millions on Wall Street. Once you finish 4 years of med school, three of IM residency, and 2 of Cards fellowship, the well will have dried up significantly for specialists who don't do fee for service (which few people are for a cath and stent). Have you considered plastics?

2) If you insist on persisting with your career plans, take Spanish now. You're going to be amazed how being bilingual in a useful language in the US sells on your med school and residency application. Because while you are going to be making less money, you are going to have a lot more Spanish speaking patients when you get out. Maybe if you grow a sense of moral responsibility to your fellow men (which should be a pre-rec for med school but sadly isn't) you'll be glad you took my advice and can converse with your patients in their native language in a culturally competent way.

FWIW, there are a lot of Spanish speaking doctors, because a lot of them ARE Spanish, and speak English as a second language (often extremely fluently).

OTOH, a school here has 17 languages that it must deal with. Try Vietnamese, Laotian, Tagalog. (Lots of Philippine nurses, but I haven't met many doctors. Perhaps they stay home.) Portuguese might be a good second string, esp. if you're on the east coast. French if you're near the Canadian border. Etc. (I didn't suggest either Chinese or Japanese, as I

in part because of the marinisma/machismo culture which inculcates the women and girls with a very strong sense of responsibility for care-giving in the family which transfers pretty well into doing it professionally too.

Honestly, that's not been my experience with Filipino nurses in the U.S. I spent several years caring for my father: he was in and out of a number of different hospitals. There were several institutions where the Filipino staff had essentially taken over the entire nursing operation. There were few left who were white, black, Chinese or anything else. I wouldn't have minded that so much, if they hadn't proven to be among the most uncaring, hostile, and sometimes outright incompetent nurses I'd ever encounte

Unfortunately for you, Indians aren't exactly flocking to the US for treatment. It's actually the other way round, since quality medical care is available for a fraction of the US price here (for those above the poverty line), which has spawned a whole "medical tourism" industry. The doctors here are as good as anywhere else in the world, and make very good money.
Most successful doctors I have known have been very compassionate people. Good luck to you, kid.

Thanks for the sanity check. Globalization doesn't just affect people that work on assembly lines.

Now that the quality of care is becoming on par, and often better than that in the US, I think it's only a matter of time before the big daddy of medical care in the US, insurance, starts moving towards cost cutting via treatment overseas. A number of insurance companies in Europe are already doing this, and NHS in the UK has a pilot voucher program going for overseas care... Only a matter of time.

You can't seriously believe that there aren't scads of premeds thinking exactly what you are? And unless cardiology practices some serious birth control like Anesthesia did, there will be a glut. Though if they do practice serious birth control to avoid a

Honestly, I love my fucking job, and would still do it, even if I won the lottery. Just would work less than 50 hours a week, instead of 80.

Exactly. I would soooo be a hobbydoc if I won the lottery. I would still do 10-15 hours a week at the ER because its fun (for the most part), but I would open a private general practice out of my house. I would see people who don't otherwise have access to care and see them the way I want to: 60 minute visits over a cup of tea, maybe even sitting in the garden if its a nice day. And I would even make a house call when its really needed. I wouldn't take money or insurance (in fact I wouldn't see insured peop

It always amazes me how science-leaning people such as those on slashdot seem to think all disease should be made to go away. Anybody who has any sense of reality knows that our species is FAR BEYOND overpopulated. I find it sickening that those who claim to have logical minds think that unnatural population levels can "be made to work".

The fact is that we need BILLIONS of people to die if the planet and its inhabitants (all living species, not just human) are ever going to have a chance. Call me sadistic, but for the sake of every other species of life on this planet... I wish the rate of heart disease was 30-60%, not 1%.

Or we could look at it from the other perspective.

Our evolutionary specialty is technology. Crisies place pressure on us to create new technology, we lose part of our species, then create the new technology and move on.

The dramatic increase in population is necessary to compel the colonization of nearby celestial bodies.

I applaud it, and hope it continues. We either adapt or die, and if we can't exercise our evolutionary niche, then it was truly limited and its time for us to go.

It always amazes me how science-leaning people such as those on slashdot seem to think all disease should be made to go away.

I think you're the guy who missed the boat. It's a generally accepted convention to treat human health as a universal good. This point came up many times in the Economist when banning tobacco in pubs was a hot button issue. There were always people pointing out that tobacco deaths saved money in the health care system. As the Economist said a number of times, we aren't in the business of evaluating human life on that premise. Almost everyone regards their own health as a positive good, so it requires a

Almost everyone regards their own health as a positive good, so it requires a considerable amount of double-think to enter into a debate with the position that aggregate human health is a net liability.

But you don't talk about aggregate statistics like that in terms of individuals. Aggregate human health isn't the issue, it's the amount of it - and the needs of that amount that is the issue.

Any argument about the carrying capacity of the planet involves unreliable extrapolations.

Okay, let me make it nice and simple without any unreliable extrapolations as you put it. Right now we are producing MUCH more greenhouse gasses than the planet is tucking away. Greenhouse gasses inevitably lead to a greenhouse effect. Please see Venus for a runaway example. Surface temperature? Cloud system? Atmospher

"Wait until the US has some sort of universal health care, and immigration from India is outlawed as a "cost cutting measure"."

Well, I'm sure even today's private insurance companies rate people based on predisposition of their race towards diseases. I"m sure blacks are rated based on things like sickle cell anemia. I seem to remember there is some jewish birth defect or something that is relatively common, etc.

I don't think it would be 'racist' to base risk scores on people due to their race, since thes

Well, I'm sure even today's private insurance companies rate people based on predisposition of their race towards diseases.

When private insurance companies are paying for your health care, the worst they can do is jack up your rate, deny claims, or not insure you at all. But the government has the power to do anything. Look at helmet laws for motorcyclists, seatbelt laws, and the myriad of others, which serve no purpose but to reduce the socialized cost of health care. Imagine what laws will be passed when the government is picking up all of the tab for everyone's health care, all in the name of reducing costs.

I seem to remember there is some jewish birth defect or something that is relatively common, etc.

Do you honestly feel the only reason to have seat belt laws is to reduce the cost of socialized medicine?

Yes, the only reason we have seat belt laws (for adults), is because of the increased accident-related costs. Why else would we have them? If someone wants to do something risky and stupid, more power to them. But if I am the one picking up the tab for the consequences, why don't I have the right to restrict such behavior?

Does the loss of life angle mean nothing to you?

Not really. Freedom to live my life in a manner of my choosing means so much more. If people want to do things which risk their lives, that's their right. Who am I to tell anyone how much

That depends. If you're in America, your odds of getting heart disease are substantially greater than if you lived in Europe. Part of that is genetics, part is exercise, part is diet, part is that Europeans don't work themselves to death.

Yes, there are probably lots of genetic markers that could increase your risk of one condition or another. There will be other genetic markers that reduce your risk. Until you know more than just one or two, you have no means of knowing what the overall effect will be.

For all you know, the last time you were given a drugs test at work, you were screened by the company for such risks. It's not like you'll ever know if they know. They're not going to tell you, all you'll know is that your premiums seem higher than normal.

So go ahead. Take the test anonymously. You can buy a "gift kit" to be delivered to a PO Box, the company doing the testing won't care. Then you will know the answer and be able to take sensible precautions (when they're known).

"For all you know, the last time you were given a drugs test at work, you were screened by the company for such risks. It's not like you'll ever know if they know. They're not going to tell you, all you'll know is that your premiums seem higher than normal."

Companies still drug test?

Man...I've not come across that since one of my first "real jobs" back in like '93 or so...none since then, and these are even on high security jobs.

And since the results are kept in secret, and since any "extras" ordered via back-handers will be doubly-secret, I don't see how anyone could ever hope to discover if the objections were honoured. There will always be plausible denial. Businesses have had thousands more years than Government to develop the perfect mix of corruption, stealth and finesse. This doesn't mean such things will happen on any given screening, what it means is that you can't ever know.

Prior to the 1920s heart disease as we know it now was almost unknown. Find a graph of its rise and it begins in the early 20th century, peaking in the 50s.

You could say much the same thing about longevity, only that seems to be peaking about now - the whole point here is that it becomes a problem later in life, which a hundred years ago wasn't such a big issue, given low life expectancy.